DESCRIPTION: Antisense oligos show promise as antitumor and antiviral agents. Antisense oligos containing all oxygens attached to the phosphodiesters (PO2) are problematic because they are unstable and degraded by endogenous nucleases, which limits their lifetime. Derivatives substituting one sulfur (POS), which are more nuclease resistant, are being explored as alternatives. Fewer studies on phosphorodithioate counterparts (PS2) have been conducted. In this proposal, the ability of PO2, POS and PS2 antisense oligos to block relevant cellular functions will be compared. Methods to improve yields of PS2 oligos will be developed. The reagent ethanedithiomonobenzoate (EDTB), which is a precursor needed to synthesize PS2 oligo, was prepared and characterized by NMR. Dr. Granger worked on synthesizing PS2-type oligos as a graduate student. Dr. Davies has familiarity with some of the biological systems to be worked (e.g., Rous sacrcoma virus, Rsv; with Erikson as a postdoctoral). The ability of PO2, POS and PS2 ability to decrease Rsv will be determined. The effect of anti-sense src oligos on foci formation, colony size and colony morphology will be studied. Analogous PO2, POS and PS2 antisense oligos will be synthesized with a particular goal of improving the overall yield.